Our data support the initiation of a relevant prospective clinical study to assess COL10A1 expression in tumors aiming to improve the management of colon cancer patients with enlarged lymph node, either by stratifying patient cohorts who do not need to receive neoadjuvant chemotherapy or minimizing the number of patients that require more comprehensive surgical attempt of D3 lymph node resection. Here, COL10A1 is linked to malignant colon neoplasm.